Graphical Abstract:

Abstract:

The brain serotonin (5-HT) and dopamine (DA) systems are targets for many clinically effective
antidepressants. Here, we studied the effects of acute administration of a new potential antidepressant
drug, 8-(trifluoromethyl)-1,2,3,4,5 - benzopentathiepin-6-amine hydrochloride (TC-2153), on
the concentration of 5-HT and DA as well as their main metabolites, 5-hydroxyindoleacetic (5-HIAA) and homovanillic
acids (HVA), in the brain. TC-2153 at the doses of 10, 20 or 40 mg/kg was administered by ip injection to adult C57BL/6
mouse males. The levels of 5-HT, 5-HIAA, DA and HVA in the hypothalamus, hippocampus, striatum, midbrain were assayed
an hour after treatment using high performance liquid chromatography with electrochemical detection. It was found
that 20 and 40 mg/kg of TC-2153 significantly increased 5-HT, 5-HIAA, DA and HVA levels as well as the HVA/DA ratio
in the hypothalamus. At the same time, the drug produced no effect on 5-HT, 5-HIAA, DA and HVA levels in the hippocampus,
striatum, midbrain or substantia nigra. Therefore, the hypothalamic 5-HT and DA systems are targets for acute
TC-2153 injection.

Abstract:The brain serotonin (5-HT) and dopamine (DA) systems are targets for many clinically effective
antidepressants. Here, we studied the effects of acute administration of a new potential antidepressant
drug, 8-(trifluoromethyl)-1,2,3,4,5 - benzopentathiepin-6-amine hydrochloride (TC-2153), on
the concentration of 5-HT and DA as well as their main metabolites, 5-hydroxyindoleacetic (5-HIAA) and homovanillic
acids (HVA), in the brain. TC-2153 at the doses of 10, 20 or 40 mg/kg was administered by ip injection to adult C57BL/6
mouse males. The levels of 5-HT, 5-HIAA, DA and HVA in the hypothalamus, hippocampus, striatum, midbrain were assayed
an hour after treatment using high performance liquid chromatography with electrochemical detection. It was found
that 20 and 40 mg/kg of TC-2153 significantly increased 5-HT, 5-HIAA, DA and HVA levels as well as the HVA/DA ratio
in the hypothalamus. At the same time, the drug produced no effect on 5-HT, 5-HIAA, DA and HVA levels in the hippocampus,
striatum, midbrain or substantia nigra. Therefore, the hypothalamic 5-HT and DA systems are targets for acute
TC-2153 injection.